molecules

Article Iron-Catalysed C(sp2)-H Enabled by Carboxylate Activation

Luke Britton 1, Jamie H. Docherty 1,*, Andrew P. Dominey 2 and Stephen P. Thomas 1,*

1 EaStCHEM School of Chemistry, University of Edinburgh, Joseph Black Building, David Brewster Road, Edinburgh EH9 3FJ, UK; [email protected] 2 GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK; [email protected] * Correspondence: [email protected] (J.H.D.); [email protected] (S.P.T.)

 Received: 30 January 2020; Accepted: 14 February 2020; Published: 18 February 2020 

Abstract: Arene C(sp2)-H bond borylation reactions provide rapid and efficient routes to synthetically versatile boronic . While iridium catalysts are well established for this reaction, the discovery and development of methods using Earth-abundant alternatives is limited to just a few examples. Applying an in situ catalyst activation method using air-stable and easily handed reagents, the iron-catalysed C(sp2)-H borylation reactions of and under blue light irradiation have been developed. Key reaction intermediates have been prepared and characterised, and suggest two mechanistic pathways are in action involving both C-H metallation and the formation of an iron boryl species.

Keywords: catalysis; borylation; Iron; C-H functionalisation; ; photochemistry

1. Introduction The development of sustainable methods for the selective C(sp2)-H functionalisation of arenes is an area of intense research but is still dominated by the use of 2nd- and 3rd-row transition metals [1–7]. Earth-abundant metals offer low toxicity and inexpensive alternatives, with iron being a leading example [8–12]. Direct C(sp2)-H borylation offers a simple and efficient route to aryl-boronic esters, which are key platforms for organic synthesis [13–15]. Iridium-based complexes have become a “go-to” for C(sp2)-H borylation reactions [16–24], while the discovery and development of Earth-abundant alternatives remains comparatively rare [25–37]. Tatsumi and Ohki showed that arenes would undergo thermally promoted C(sp2)-H borylation using an N-heterocyclic carbene cyclopentadienyl iron(II) alkyl complex [NHC(Cp*)FeMe] as a catalyst in the presence of tert-butylethylene (Scheme1a) [ 35]. Mankad applied heterobimetallic Fe-Cu and Fe-Zn complexes under continuous ultraviolet light irradiation to arene C(sp2)-H borylation [36]. Similarly, Darcel and co-workers reported the use of a bis(diphosphino) iron(II) dialkyl and dihydride complexes for arene C(sp2)-H borylation, again under continuous ultraviolet light irradiation [37]. While these landmark reports are highly significant developments, all require the prior synthesis of sensitive inorganic complexes which are synthetically challenging and difficult to handle for the non-specialist practitioner, thus limiting use by the broader synthetic community.

Molecules 2020, 25, 905; doi:10.3390/molecules25040905 www.mdpi.com/journal/molecules Molecules 2020, 25, 905 2 of 11 Molecules 2020, 25, x FOR PEER REVIEW 2 of 12

SchemeScheme 1. Iron-catalysed 1. Iron-catalysed C-H C-H borylation borylation of arenes.of arenes. (a )(a Prior) Prior approaches approaches to to iron-catalysed iron-catalysed C( C(spsp22)-H-bond)-H- borylationbond borylation with pinacolborane with pinacolborane (HBpin) (HBpin) using organoiron using organoiron and iron and/copper iron/copper bimetallic bimetallic catalysts. catalysts. (b) This (b) This 2work: C(sp2)-H bond borylation using dmpe2FeCl2 as a pre-catalyst, activated by exogenous work: C(sp )-H bond borylation using dmpe2FeCl2 as a pre-catalyst, activated by exogenous , under blue light irradiation. nucleophiles, under blue light irradiation. To reduce the synthetic challenges, and need for organometallic reagents, we questioned To reduce the2 synthetic challenges, and need for organometallic reagents, we questioned whether the C(2sp )-H borylation chemistry reported previously could be simplified by in situ catalyst whetheractivation the C(usingsp )-H only borylation bench stable chemistry reagents. In reported the example previously reported by could Darcel be and simplified co-workers by the in situ catalystbis[1,2-bis(dimethylphosphino)ethane- activation using only bench stableP,P′]dimethyliron(II) reagents. In thepre-catalyst example reported(dmpe2FeMe by2) Darcelwas and co-workersgenerated the by bis[1,2-bis(dimethylphosphino)ethane- the addition of methyllithium to theP ,Pcorresponding0]dimethyliron(II) iron(II) pre-catalyst dichloride (dmpe complex2FeMe 2) was generated(dmpe2FeCl2 by) [37]. the additionSimilarly, of methyllithiumthe catalytically to active the corresponding bis[1,2-bis(dimethylphosphino)ethane- iron(II) dichloride complex (dmpeP,2PFeCl′]iron(II)2)[37 dihydride]. Similarly, (dmpe the2FeH catalytically2) could be active accessed bis[1,2-bis(dimethylphosphino)ethane- using either LiHBEt3 or LiAlH4 [37,38].P Given,P0]iron(II) our previous work on the in situ generation of hydride donors formed by the combination of alkoxide dihydride (dmpe2FeH2) could be accessed using either LiHBEt3 or LiAlH4 [37,38]. Given our previous worksalts on theand inpinacolborane situ generation (HBpin) of hydride[39], we postulated donors formed that the by active the combinationC(sp2)-H borylation of alkoxide pre-catalyst, salts and dmpe2FeH2, may be accessible by the same method. Reaction of2 substoichiometric alkoxide salt with pinacolborane (HBpin) [39], we postulated that the active C(sp )-H borylation pre-catalyst, dmpe2FeH2, HBpin, the source used for this borylation, would generate a hydride reductant in situ to may be accessible by the same method. Reaction of substoichiometric alkoxide salt with HBpin, the activate the dmpe2FeCl2 pre-catalyst to dmpe2FeH2, the active borylation catalyst, and thus initiate boron source used for this borylation, would generate a hydride reductant in situ to activate the catalysis. Importantly, the dmpe2FeCl2 complex displays much greater air- and moisture stability dmpecompared2FeCl2 pre-catalyst to the dihydride to dmpe and2 FeHdialkyl2, theanalogues. active borylationHerein, we catalyst,report the and in thussitu activation initiate catalysis. of Importantly,dmpe2FeCl the2 and dmpe application2FeCl2 complexto the C(sp displays2)-H borylation much reaction greater of air- heteroarenes and moisture (Scheme stability 1b). compared to the dihydride and dialkyl analogues. Herein, we report the in situ activation of dmpe2FeCl2 and application2. Results to the C(sp2)-H borylation reaction of heteroarenes (Scheme1b). Guided by the work of Darcel and co-workers, we selected 2-methylfuran 2a as an ideal test 2. Results substrate for our investigations. Darcel and co-workers showed that dmpe2FeMe2 could be used as a Guidedpre-catalyst by for the the work borylation of Darcel of andfuran co-workers, 2a (3 equiv.) we using selected HBpin 2-methylfuran (1 equiv.) under2a ascontinuous an ideal test substrate for our investigations. Darcel and co-workers showed that dmpe FeMe could be used as a 2 2 pre-catalyst for the borylation of 2a (3 equiv.) using HBpin (1 equiv.) under continuous ultraviolet light irradiation to give a regioisomeric mixture of 5- and 4-borylated furans, 3a and 4a respectively Molecules 2020, 25, 905 3 of 11 Molecules 2020, 25, x FOR PEER REVIEW 3 of 12

(67%,ultraviolet3a:4a = 82:18) light irradiation [37]. Using to ourgive alkoxide a regioisomeric activation mixture strategy of 5- we and found 4-borylated the use furans, of ultraviolet 3a and 4a light for thisrespectively reaction was (67%, not necessary,3a:4a = 82:18) instead [37]. operatingUsing our alkoxide with lower activation energy strategy blue light we (Kessil found A160the use WE, of 40 W Blueultraviolet LED). Additionally, light for this we reaction used anwas inverted not necessar stoichiometryy, instead operating of arene with (1 equiv.) lower andenergy HBpin blue (1.2light equiv) and(Kessil a reduced A160 catalyst WE, 40 W loading. Blue LED). Using Additionally, these reaction we us parameters,ed an inverted we stoichiometry assessed the of arene ability (1 ofequiv.) a selection and HBpin (1.2 equiv) and a reduced catalyst loading. Using these reaction parameters, we assessed of potential activators to initiate catalysis alongside the dmpe2FeCl2 1 pre-catalyst. (Scheme2). the ability of a selection of potential activators to initiate catalysis alongside the dmpe2FeCl2 1 pre- Any of LiOMe, KOMe, TBAOMe (TBA = tetra-n-butylammonium), NaOiPr, NaOtBu or KOtBu catalyst. (Scheme 2). triggeredAny pre-catalyst of LiOMe, activationKOMe, TBAOMe and the (TBA formation = tetra-n of-butylammonium), both furyl boronic NaO esteriPr, NaO regioisomers,tBu or KOtBu3a and 4a, albeittriggered in modestpre-catalyst yields activation (17% and to 39%) the format and withion of varying both furyl regioselectivity, boronic regioisomers, after 24 h. 3a The and use of carboxylate4a, albeit salts in modest also initiated yields (17% catalysis; to 39%) NaO and2CH, with LiOAc, varying NaOAc, regioselectivity, Na(2-EH) after (2-EH 24= h.2-ethylhexanoate), The use of TBA(2-EH),carboxylate NaO salts2CPh, also NaO initiated2CCF3 allcatalysis; successfully NaO2CH, initiated LiOAc, catalysis NaOAc, with Na(2-EH) varying (2-EH efficiency = 2- (2% to 45%).ethylhexanoate), Na(2-EH) and TBA(2-EH), NaO2CPh NaO outperformed2CPh, NaO2CCF all alkoxide3 all successfully salts, and initiated the yields catalysis obtained with varying using these activatorsefficiency could (2% be to increased45%). Na(2-EH) with prolonged and NaO2CPh reaction outperformed times to giveall alkoxide a mixture salts, of and furyl the boronic yields esters 3a andobtained4a in using good these yield activators and regioselectivity could be increased (Na(2-EH), with prolonged 59%, 3a: 4areaction= 71:29). times Control to give a reactions mixture with of furyl boronic esters 3a and 4a in good yield and regioselectivity (Na(2-EH), 59%, 3a:4a = 71:29). no catalyst, no added activator, and with no light irradiation showed no reactivity, highlighting the Control reactions with no catalyst, no added activator, and with no light irradiation showed no necessity of each reaction component. reactivity, highlighting the necessity of each reaction component.

Scheme 2. Activator screening for the borylation of 2-methyl furan by dmpe2FeCl2 1. a Yieldsa Scheme 2. Activator screening for the borylation of 2-methyl furan by dmpe2FeCl2 1. Yields 1 determineddetermined by by1H-NMR H-NMR spectroscopy spectroscopy of the the crude crude reaction reaction mixtures mixtures using using 1,3,5-trimethoxybenzene 1,3,5-trimethoxybenzene 1 as anas internalan internal standard. standard. ProductProduct ratios were were determined determined by byH-NMR1H-NMR spectroscopy spectroscopy of the of crude the crude reaction mixtures. b Reaction time = 15 h. c Reaction time = 48 h. 2-EH = 2-ethylhexanoate. TBA = tetra- reaction mixtures. b Reaction time = 15 h. c Reaction time = 48 h. 2-EH = 2-ethylhexanoate. TBA = n-butylammonium. tetra-n-butylammonium.

2.1.2.1. Substrate Substrate Scope Scope With optimised reaction conditions established using dmpe2FeCl2 (4 mol%), Na(2-EH) (8 mol%), With optimised reaction conditions established using dmpe FeCl (4 mol%), Na(2-EH) (8 mol%), arene (1.0 equiv.) and HBpin (1.2 equiv.) in THF under blue light2 irradiation,2 we assessed the arenereactivity (1.0 equiv.) of the and system HBpin by application (1.2 equiv.) to in aTHF subset under of furan blue and light irradiation, derivatives we assessed (Scheme the 3). reactivity 2- of theMethylfuran system by application2a underwent to aefficient subset ofborylation furan and tothiophene generate a derivatives mixture of (Scheme 5- and3 ).4-borylated 2-Methylfuran 2a underwentregioisomers effi 3acient and borylation4a in good toyield generate and regios a mixtureelectivity of (72%, 5- and 81:19). 4-borylated The parent, regioisomers unsubstituted3a and 4a in goodfuran yield 2b, also and underwent regioselectivity successful (72%, borylation 81:19). Thebut gave parent, a regioisomeric unsubstituted mixture furan of2b the, also 2- and underwent 3- successfulsubstituted borylation boronic ester but regioisomers gave a regioisomeric 3b and 4b, and mixture additionally of the th 2-e bis-boryl and 3-substituted furans 5b. Borylation boronic ester regioisomers 3b and 4b, and additionally the bis-boryl furans 5b. Borylation of 2,3-dimethylfuran 2c gave the corresponding 5-boryl regioisomer 3c exclusively in good yield. 2-Ethylfuran 2d reacted similarly to the 2-methylfuran analogue 2a giving a mixture of 4- and 5-substituted boronic esters 3d Molecules 2020, 25, x FOR PEER REVIEW 4 of 12

Molecules 2020, 25, 905 4 of 11 of 2,3-dimethylfuran 2c gave the corresponding 5-boryl regioisomer 3c exclusively in good yield. 2- Ethylfuran 2d reacted similarly to the 2-methylfuran analogue 2a giving a mixture of 4- and 5- and substituted4d. Unfortunately, boronic esters application 3d and to4d. thiophenes Unfortunately, demonstrated application to limited thiophenes reactivity demonstrated under the limited established reactivity under the established reaction conditions, giving only low yields of boryl-arenes 3e-g and reaction conditions, giving only low yields of boryl-arenes 3e-g and 4e-g, again as a mixture of 4e-g, again as a mixture of regioisomers, and bis-borylated product when the parent thiophene was regioisomers,used [40]. and bis-borylated product when the parent thiophene was used [40].

Scheme 3. Na(2-EH) activated borylation of furan and thiophene derivatives using dmpe2FeCl2 1. aa Scheme 3. Na(2-EH) activated borylation of furan and thiophene derivatives using dmpe2FeCl2 1. Yields 1 determinedYields determined by 1H-NMR by spectroscopy H-NMR spectroscopy of the crude reactionof the mixturescrude reaction using1,3,5-trimethoxybenzene mixtures using 1,3,5- as an trimethoxybenzene as an internal standard. Product ratios were determined by 1H-NMR internal standard. Product ratios were determined by 1H-NMR spectroscopy of the crude reaction mixtures. spectroscopy of the crude reaction mixtures. b Values represent the ratio of 2-boryl:3-boryl:bis-boryl b Values represent the ratio of 2-boryl:3-boryl:bis-boryl products. products. 2.2. Mechanistic Investigations 2.2. Mechanistic Investigations On the basis of successful catalysis we presumed that our in situ activation system provided On the basis of successful catalysis we presumed that our in situ activation system provided access to the active iron(II) dihydride complex dmpe FeH 7, which had been shown to be catalytically access to the active iron(II) dihydride complex dmpe2 22FeH2 7, which had been shown to be activecatalytically by Darcel active and co-workersby Darcel and [37 co-workers]. To support [37]. this, To support we combined this, we eachcombined component each component in the absence in of lightthe or absence arene, i.e.,of light the or reaction arene, i.e., of the dmpe reaction2FeCl of2 1dmpe, Na(2-EH)2FeCl2 1, andNa(2-EH) HBpin and (Scheme HBpin (Scheme4a). This 4a). showed This the formationshowed of the both formation the monohydride of both the monohydride product dmpe product2FeHCl dmpe6 and2FeHCl the 6 expected and the expected dihydride, dihydride, dmpe2 FeH2 7, asdmpe observed2FeH2 by7, as31 observedP-NMR spectroscopyby 31P-NMR spectroscopy (see Supplementary (see Supplementary Materials, Materials, S16). Reaction S16). Reaction of the activator, of Na(2-EH),the activator, and HBpinNa(2-EH), in theand absenceHBpin in ofthe pre-catalyst absence of pre-catalyst showed ligand showed redistribution ligand redistribution to a mixture to a of mixture of boron-containing species, including boron “ate” complexes, BH3 and- [BH4]-, as observed11 boron-containing species, including boron “ate” complexes, BH3 and [BH4] , as observed by B-NMR by 11B-NMR spectroscopy (see Supplementary Materials, S3). This reactivity is in accordance with spectroscopy (see Supplementary Materials, S3). This reactivity is in accordance with that when using that when using other nucleophiles such as alkoxide salts [39,41]. Taken together, these observations other nucleophiles such as alkoxide salts [39,41]. Taken together, these observations are indicative are indicative of an in situ activation process, whereby the added carboxylate reagent Na(2-EH) of an in situ activation process, whereby the added carboxylate reagent Na(2-EH) triggers hydride triggers hydride transfer from boron to iron to form the dihydride dmpe2FeH2 7. Once formed, the transferiron dihydride from boron dmpe to2 ironFeH2 to7 can form efficiently the dihydride catalyse the dmpe C(sp22FeH)-H borylation2 7. Once reaction. formed, the iron dihydride 2 dmpe2FeH2 7 can efficiently catalyse the C(sp )-H borylation reaction.

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SchemeScheme 4. (4.a )(a Pre-catalyst) Pre-catalyst activation activation andand hydride formation. formation. (b) (bMechanistic) Mechanistic investigations investigations of of dmpe2FeH2 7 produced by hydride transfer from HBpin and Na(2-EH). dmpe2FeH2 7 produced by hydride transfer from HBpin and Na(2-EH).

As the dihydride complex dmpe2FeH2 7 was readily formed using our in situ hydride transfer method, and was observable by 1H and 31P-NMR spectroscopy, we next investigated the fundamental steps of this borylation reaction with the aim of identifying key reaction intermediates. Reaction of the in situ generated dmpe2FeH2 7 with excess HBpin under blue light irradiation led to the formation of both cis-dmpe2FeH(Bpin) 8 and trans-dmpe2FeH(Bpin) 9 boryl iron complexes, as observed by 1H, 11B, and 31P NMR spectroscopy (see Supplementary Materials, S17-19). These complexes were previously reported by Darcel and co-workers, where they were formed from the reaction of the related dialkyl complex, dmpe2FeMe2, with HBpin [37]. Addition of 2-methylfuran 2a to the mixture of cis-dmpe2FeH(Bpin) 8 and trans-dmpe2FeH(Bpin) 9 under blue light irradiation gave the formation Molecules 2020, 25, 905 6 of 11 of the regioisomeric furyl boronic esters 3a and 4a (3a:4a = 71:29), notably in a different ratio to that observed during catalysis (vide supra, 3a:4a = 81:19). Blue light irradiation of the dihydride complex dmpe2FeH2 7 in the presence of excess 2-methylfuran 2a led to exclusive C(sp2)-H bond metallation at the 5-position to give 1 31 trans-dmpe2FeH(2-Me-furyl) 10, as observed by H and P NMR spectroscopy (see Supplementary Materials, S22-24). Addition of HBpin to trans-dmpe2FeH(2-Me-furyl) 10 and irradiation with blue light induced formation of the furyl boronic esters 3a and 4a (3a:4a = 90:10). Again, in a different ratio to that observed under catalysis. As the ratio of regioisomers observed under catalytic conditions (3a:4a = 81:19) appears to be a combination of the ratios observed in the stoichiometric studies (3a:4a = 71:29, and 90:10 respectively), it is suggestive that both the C-H metallation and iron boryl pathways are operative. 2 Specifically, the reaction can precede by C(sp )-H bond metallation to give dmpe2FeH(2-Me-Furyl) 10, followed by C(sp2)-B bond formation, or by direct reaction of arene with the iron boryl species cis-dmpe2FeH(Bpin) 8 and trans-dmpe2FeH(Bpin) 9. The relative ratios of the furyl boronic ester regioisomers indicate both pathways are equally accessible for the activated catalyst. (53% by C-H metallation, 47% by the iron boryl species).

3. Conclusions In summary, we have investigated the applicability of several alkoxide, carboxylate and other, common bench stable reagents towards the in situ activation of an iron(II) pre-catalyst for C(sp2)-H bond borylation. We found a sodium carboxylate salt Na(2-EH) in combination with HBpin to be a potent pre-catalysts activator generating the iron dihydride dmpe2FeH2 7 in situ. The validity of this method was demonstrated by the generation of catalytically relevant species that were used as mechanistic probes. These suggest two C-H borylation pathways are operating to give the aryl boronic ester products; C-H metallation followed by borylation, and formation of an iron boryl species followed by arylation.

4. Materials and Methods

4.1. General Information All compounds reported in the manuscript are commercially available or have been previously described in the literature unless indicated otherwise. All experiments involving iron were performed using standard Schlenk techniques under argon or nitrogen atmosphere. All yields refer to yields determined by 1H-NMR spectroscopy of crude reaction mixtures using an internal standard. All product ratios refer to product ratios determined by 1H-NMR spectroscopy of the crude reaction mixtures. 1H-NMR and 13C-NMR data are given for all compounds when possible in the experimental section for characterisation purposes. Spectroscopic data matched those reported previously.

4.2. Activator Synthesis

Tetra-n-butylammonium 2-ethylhexanoate TBA(2-EH)

A suspension of KH (80 mg, 2 mmol) in anhydrous THF (20 mL) was prepared under an N2 atmosphere, 2-ethylhexanoic acid (0.32 mL, 2 mmol) was added dropwise whilst stirring. n.b. gas evolution (H2). The solution was stirred for 3 h at room temperature, and the THF removed in vacuo to give an amorphous colourless solid. The solid was re-dissolved in MeOH (20 mL) and tetra-n-butylammonium chloride (556 mg, 2 mmol) was added, the solution was stirred for 16 h, filtered through a glass frit and dried in vacuo without further purification to give tetra-n-butylammonium 2-ethylhexanoate (0.72 g, 1.86 mmol, 93%) as an amorphous white solid.

1 H-NMR (500 MHz, CDCl3) δ 3.51–3.35 (m, 8H), 2.09 (tt, J = 8.4, 5.4 Hz, 1H), 1.66 (m, 8H), 1.62–1.54 (m, 2H), 1.48–1.39 (m, 8H), 1.39–1.23 (m, 6H), 0.98 (t, J = 7.3 Hz, H), 0.91 (t, J = 7.4 Hz, 3H), 0.88–0.82 (m, 13 3H). C-NMR (126 MHz, CDCl3) δ 181.2, 59.0, 51.1, 33.1, 30.5, 26.4, 24.3, 23.2, 19.8, 14.2, 13.7, 12.7. Molecules 2020, 25, 905 7 of 11

4.3. Pre-catalyst Synthesis dmpe2FeCl2 1 [42] Anhydrous iron dichloride (0.21 g, 1.67 mmol) was charged to a Schlenk flask and dissolved in anhydrous THF (10 mL), dmpe [(bis(dimethylphosphino)ethane]; 0.50 g, 3.33 mmol) were added to the flask under an Ar atmosphere and the solution left to stir for 48 h at room temperature. The solvent was removed in vacuo, and in an argon-filled glove box, the residue was re-dissolved in dichloromethane (5 mL) and filtered through glass wool. The filtrate was reduced in vacuo to produce a green amorphous solid (0.549 g, 1.29 mmol, 77%).

1 8 31 H-NMR (400 Hz, d -THF) δ 2.18 (s, 8H), 1.42 (s, 24H). P-NMR (202 MHz, CDCl3) δ 59.0.

4.4. General Borylation Procedure

In an argon-filled glovebox, dmpe2FeCl2 1 (8.6 mg, 0.02 mmol), sodium 2-ethylhexanoate (6.6 mg, 0.04 mmol), HBpin (87 µL, 0.6 mmol), substrate (0.5 mmol), and THF (1 mL) were added to a 1.7 mL sample vial and shaken to ensure full dissolution. The vial was placed under blue light radiation for 48 h and then allowed to cool to room temperature. Yields determined by 1H-NMR spectroscopy of the crude reaction mixtures using 1,3,5-trimethoxybenzene as an internal standard [0.5 mL; standard solution = 1,3,5-trimethoxybenzene (0.336 g, 2.0 mmol) in diethyl (10 mL)]. Product ratios were determined by 1H-NMR spectroscopy of the crude reaction mixtures.

4.5. Characterisation of Borylated Products

4.5.1. 2-Methylfuran Derivatives

4,4,5,5-Tetramethyl-2-(5-methylfuran-2-yl)-1,3,2-dioxaborolane 3a [37], 4,4,5,5-tetramethyl-2-(5- methylfuran-3-yl)- 1,3,2-dioxaborolane 4a [37] Following the general procedure; 2-methylfuran 2a (41 mg, 44 µL, 0.5 mmol). Yield = 72%. 3a:4a = 1 81:19. H-NMR (500 MHz, CDCl3) 3a: δ 6.99 (d, J = 3.2 Hz, 1H), 6.06–6.01 (m, 1H), 2.36 (s, 3H), 1.34 (s, 12H). 4a: δ 7.62 (d, J = 0.9 Hz, 1H), 6.15 (t, J = 1.0 Hz, 1H), 2.29 (d, J = 1.1 Hz, 3H), 1.31 (s, 12H). 13 C-NMR (126 MHz, CDCl3) 3a: δ 157.8, 124.8, 106.9, 84.0, 24.7, 13.9. 4a: δ 152.7, 149.7, 108.8, 83.3, 24.9, 11 13.1. B-NMR (160 MHz, CDCl3) 3a: δ 27.1. 4a: δ 29.8.

4.5.2. Furan Derivatives

4,4,5,5-Tetramethyl-2-(furanyl-2-yl)-1,3,2-dioxaborolane 3b [43], 4,4,5,5-tetramethyl-2-(furanyl- 3-yl)-1,3,2-dioxaborolane 4b [44], 2,5-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)furan 5ba [45], 2,4-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)furan 5bb [45] Following the general procedure; furan 2b (34 mg, 36 µL, 0.5 mmol). Yield = 52%. 3b:4b:5ba:5bb 1 60:21:4:5. H-NMR (600 MHz, CDCl3) 3b: δ 7.65 (d, J = 1.7 Hz, 1H), 7.07 (d, J = 3.4 Hz, 1H), 6.44 (dd, J = 3.4, 1.6 Hz, 1H), 1.35 (s, 12H). 4b: δ 7.78 (s, 1H), 7.46 (m, J = 1.6 Hz, 1H), 6.59 (d, J = 1.7 Hz, 1H), 1.32 (s, 1H). 5ba: δ 7.06 (s, 2H), 1.33 (s, 24H). 5bb: δ 7.78 (s, 1H), 7.28 (s, 1H), 1.30 (s, 24H). 13C-NMR (126 MHz, CDCl3) 3b: δ 147.3, 123.2, 110.3, 84.2, 24.8. 4b: δ 151.2, 142.9, 113.1, 83.5, 24.9. 5ba: δ 123.2, 83.5, 11 24.8. 5bb: δ 151.2, 83.2, 75.1, 24.6. B-NMR (160 MHz, CDCl3) 3b: δ 27.2. 4b: δ 29.8.

4.5.3. 2.3-Dimethylfuran Derivatives

4,4,5,5-Tetramethyl-2-(4,5-dimethylfuran-2-yl)-1,3,2-dioxaborolane 3c [46] Molecules 2020, 25, 905 8 of 11

Following the general procedure; 2,3-dimethylfuran 2c (48 mg, 53 µL, 0.5 mmol). Yield = 46%. 3c:4c = 1 13 100:0. H-NMR (500 MHz, CDCl3) δ 6.87 (s, 1H), 2.26 (s, 3H), 1.94 (s, 3H), 1.33 (s, 12H). C-NMR (126 11 MHz, CDCl3) δ 153.4, 127.1, 115.2, 83.9, 24.7, 11.8, 9.7. B-NMR (160 MHz, CDCl3) δ 27.2.

4.5.4. 2-Ethylfuran Derivatives

4,4,5,5-Tetramethyl-2-(5-ethylfuran-2-yl)-1,3,2-dioxaborolane 3d [47], 4,4,5,5-tetramethyl-2- (5-methylfuran-3-yl)-1,3,2-dioxaborolane 4d [47] Following the general procedure; 2-ethylfuran 2d (48 mg, 53 µL, 0.5 mmol). Yield = 59%. 3d:3d = 70:30. 1 H-NMR (500 MHz, CDCl3) 3d: δ 7.01 (d, J = 3.3 Hz, 1H), 6.05 (d, J = 3.1, 1H), 2.72 (q, J = 7.6 Hz, 2H), 1.34 (s, 12H), 1.25 (m, 3H). 4d: δ 7.64 (d, J = 0.8 Hz, 1H), 6.18 (d, J = 1.1 Hz, 1H), 2.6 (q, J = 7.5, 2H), 1.31 13 (s, 12H), 1.25 (m, 3H). C-NMR (126 MHz, CDCl3) 3d: δ 163.6, 124.7, 105.2, 84.0, 24.7, 21.6, 12.2. 4d: δ 11 163.6, 149.6, 107.2, 83.3, 24.9, 21.1, 12.1. B-NMR (160 MHz, CDCl3) 3d: δ 27.2. 4d: δ 29.9.

4.5.5. 2-Methylthiophene Derivatives

4,4,5,5-Tetramethyl-2-(5-methylthiophen-2-yl)-1,3,2-dioxaborolane 3e [47], 4,4,5,5-tetramethyl-2 -(5-methylthiophen-3-yl)-1,3,2-dioxaborolane 4e [47] Following the general procedure; 2-methylthiophene 2e (49 mg, 48 µL, 0.5 mmol). Yield = 9%. 3e:4e = 1 66:34. H-NMR (500 MHz, CDCl3) 3e: δ 7.45 (d, J = 3.4 Hz, 1H), 6.84 (d, J = 3.4, 1H), 2.53 (s, 3H), 1.33 (s, 12H). 4e: δ 7.67 (d, J = 1.2 Hz, 1H), 7.04 (s, 1H), 2.49 (d, J = 1.1 Hz, 3H), 1.32 (s, 12H). 13C-NMR (126 11 MHz, CDCl3) 3e: δ 147.5, 137.6, 127.0, 83.9, 24.9, 15.4. 4e: not observed. B-NMR (160 MHz, CDCl3) δ 28.7.

4.5.6. Thiophene Derivatives

4,4,5,5-Tetramethyl-2-(thiophen-2-yl)-1,3,2-dioxaborolane 3f [48], 4,4,5,5-tetramethyl-2-(thiophen-3 -yl)-1,3,2-dioxaborolane 4f [49], 2,5-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene 5f [48] Following the general procedure; thiophene 2f (42 mg, 40 µL, 0.5 mmol). Yield = 11%. 3f:4f:5f = 27:9:64. 1 H-NMR (500 MHz, CDCl3) 3f: δ 7.64 (m, 1H), 7.63 (d, J = 4.8 Hz, 1H), 7.19 (d, J = 4.8 Hz, 1H), 1.35 (s, 12H). 4f: δ 7.92 (d, J = 2.6 Hz, 1H), 7.41 (d, J = 4.9 Hz, 1H), 7.34 (dd, J = 4.8, 2.7 Hz, 1H), 1.35 (s, 12H). 5f: 13 δ 7.66 (s, 2H), 1.34 (s, 24H). C-NMR (126 MHz, CDCl3) 3f: δ 137.2, 132.4, 128.2, 83.2, 24.9. 4f: δ 136.5, 11 129.0, 125.3, 83.2, 24.8. 5f: δ 137.7, 84.1, 24.8. B-NMR (160 MHz, CDCl3) δ 29.2.

4.5.7. 3-Methylthiophene Derivatives

4,4,5,5-Tetramethyl-2-(4-methylthiophen-2-yl)-1,3,2-dioxaborolane 3g [17] Following the general procedure; 3-methylthiophene 2g (49 mg, 48 µL, 0.5 mmol). Yield = 4%. 3g:4g = 1 100:0. H-NMR (500 MHz, CDCl3) δ 7.44 (d, J = 1.2 Hz, 1H), 7.19 (t, J = 1.1 Hz, 1H), 2.29 (d, J = 0.9 Hz, 13 11 3H), 1.34 (s, 12H). C-NMR (126 MHz, CDCl3) δ 139.5, 139.0, 128.2, 84.0, 24.9, 15.1. B-NMR (160 MHz, CDCl3) δ 29.1.

4.6. Mechanistic Investigations dmpe2FeH2 7 [37] dmpe2FeCl2 1 (10 mg, 0.023 mmol), sodium 2-ethylhexanoate (7.6 mg, 0.046 mmol), and HBpin (7 µL, 0.046 mmol) were added to a Young’s NMR tube under an Ar atmosphere and heated at 60 ◦C for 3 days. 1H-NMR (600 MHz, THF) δ 14.38 (m). 31P-NMR (500 MHz, THF) δ 76.9 (t, J = 28 Hz), 67.7 (t, − J = 28 Hz). cis-dmpe2FeH(Bpin) 8 and trans-dmpe2FeH(Bpin) 9 [37] Molecules 2020, 25, 905 9 of 11

dmpe2FeCl2 1 (4.3 mg, 0.001 mmol), sodium 2-ethylhexanoate (3.3 mg, 0.002 mmol), and HBpin (87 µL, 0.6 mmol) were added to a Young’s NMR tube under an Ar atmosphere and irradiated with blue light for 16 h. 1H-NMR (500 MHz, THF) δ 13.1 (p, J = 43.2 Hz), 14.0 (m). 31P-NMR (500 MHz, THF) δ − − 77.6(m), 77.2 (m), 59.7 (m), 58.9 (m). dmpe2FeH(2-Me-furyl) 10 dmpe2FeCl2 1 (10 mg, 0.023 mmol), sodium 2-ethylhexanoate (30.4 mg, 0.184 mmol), and HBpin (7 µL, 0.046 mmol) were added to a Young’s NMR tube under an Ar atmosphere and warmed at 60 ◦C for 24 h. 2-methylfuran (8 µL, 0.092 mmol) was added under an Ar atmosphere and the sample irradiated with blue light for 3 h. This complex was observed in situ. 1H-NMR (500 MHz, THF) δ -18.93 (q, J = 45.8 Hz). 31P-NMR (500 MHz, THF) δ 77.1 (d, J = 38.1 Hz). MS: (HRMS – EI+) Found 438.12041 56 (C17H38O1 Fe1P4), requires 438.12171.

Supplementary Materials: The following are available online. Author Contributions: L.B. and J.H.D. carried out the experimental work. J.H.D., A.P.D. and S.P.T. conceived and supervised the project. L.B., J.H.D., and S.P.T. wrote the paper. All authors have read and agreed to the published version of the manuscript. Funding: This research was funded by The Royal Society, UF130393 and RF191015, and GSK/EPSRC, PIII0002. Acknowledgments: S.P.T. acknowledges the University of Edinburgh and the Royal Society for a University Research Fellowship. J.H.D. and S.P.T. acknowledge GSK, EPSRC, and the University of Edinburgh for post-doctoral funding. L.B. acknowledges the Royal Society and the University of Edinburgh for a PhD studentship. Conflicts of Interest: The authors declare no conflict of interest.

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Sample Availability: Samples of the pre-catalyst 1 are available from the authors.

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